Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats

doi:10.1016/j.cardiores.2005.05.023

Cardiovascular Research 2005 68(1):118-127; doi:10.1016/j.cardiores.2005.05.023

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Different effects of long- and short-acting loop diuretics on survival rate in Dahl high-salt heart failure model rats

Junichi Yoshida^a^,b, Kazuhiro Yamamoto^a^,*, Toshiaki Mano^a^,b, Yasushi Sakata^a^,b, Mayu Nishio^a^,b, Tomohito Ohtani^a^,b, Masatsugu Hori^a, Takeshi Miwa^b and Tohru Masuyama^c

^aDepartment of Cardiovascular Medicine, (A8) Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Japan
^bGenome Information Research Center, Osaka University, Suita, Japan
^cCardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

^* Corresponding author. Tel.: +81 6 6879 6612; fax: +81 6 6879 6613. Email address: kazuhiro{at}medone.med.osaka-u.ac.jp

Objectives: We compared therapeutic effects of furosemide, ashort-acting loop diuretic, and azosemide, a long-acting one,in hypertensive heart failure rats to test the hypothesis thatlong-acting diuretics are superior to short-acting types inheart failure.

Methods: Dahl salt-sensitive rats fed an 8% NaCl diet from age8 weeks were divided at age 21 weeks (compensated hypertrophicstage) into three groups: rats treated with furosemide (40 mg/kg/day),those treated with azosemide (80 mg/kg/day) and untreated rats.Rats fed a 0.3% NaCl diet served as controls.

Results: Both medications prevented left ventricular systolicdysfunction and enlargement at age 31 weeks, and attenuatedmacrophage infiltration, reactive oxygen species generation,and gelatinolytic activity to the same degree. Azosemide suppressedleft ventricular fibrosis to the control level, but furosemidedid not. Azosemide ameliorated myocardial catecholamine depletionand improved survival rate. Furosemide increased plasma norepinephrinelevels and did not exert such beneficial effects.

Conclusions: Azosemide provided better prognosis in heart failurerats compared with furosemide, partly through attenuation ofthe reflex increase in cardiac sympathetic neuronal activitycaused by the development of heart failure. The current findingssuggest a need for clinical trials examining whether long- andshort-acting diuretics provide a different prognosis in patientswith heart failure.

KEYWORDS Antihypertensive/diuretic agents; Heart failure; Hormones

Time for primary review 28 days

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